Ochratoxins are known compounds. They are toxic metabolites known to be produced from some strains of the fungus Aspergillus ochraceus. Interest in the ochratoxins, and particularly ochratoxins A, B and C, is prompted by the health hazard they pose because of their occurrence in agricultural products such as silage, hay, feedstuffs and corn. That is to say, the spores of the Aspergillus ochraceus fungus are present in these materials; and, if the right fermenting moisture and temperature conditions occur the resulting metabolism decomposition products include the ochratoxins. Thus, they may occur in nature, in foodstuffs which enter the food chain ultimately leading to man. It is known that the ochratoxins may cause kidney lesions, ultimately leading, in acute cases, to renal failure.
However, because there never has been a practical synthesis route for the ochratoxins, it has been difficult to isolate and study them in the laboratory. Such studies are desirable for determining the precise effects of each ochratoxin compound, for determining possible anti-toxins, and for determining the residue effect on the food chain.
While some ochratoxins may be obtained in small microgram quantities from the fermentation of Aspergillus ochraceus, it is difficult to obtain the pure compounds. Thus one never knows for sure, in controlled studies using fermentation extract, whether it is in fact the effect of the ochratoxins which is being studied. Moreover, the sparing availability of the pure compounds has made it virtually impossible for any meaningful anti-toxin studies, or residue studies.
There have in the past been previously reported literature routes for the synthesis of some Ochratoxins; see, for example: Steyn, P. S.; Holzapfel, C. W., Tetrahedron, 1967, 23, 4449; and Roberts, J. C.; Woollven, P. J. Chem. Soc. C., 1970, 278. However, these are not practical, involve a multitude of lengthy, complex steps and some very expensive chemicals, such as silver compounds.
Thus, it can be seen that there is a real and continuing need for a simple, direct and inexpensive synthesis route for Ochratoxins. The availability of the pure compounds in quantity would allow for toxin and anti-toxin studies, biological activity testing, and residue studies.
The primary object of this invention is to fulfill this continuing need.
The method and manner of accomplishing this primary objective, as well as others, will become apparent from the detailed description of the invention which follows.